1. Field of the Invention
The present invention relates to osmotically controlled implantable delivery devices, and more particularly to a delivery system having a membrane material that controls the delivery rate of a beneficial agent from the delivery system, in which the membrane material is cast, calendered or extruded, then machined (i.e., stamped, die cut or otherwise cut to shape), and the membrane material is maintained within the delivery device by a retaining means.
2. Description of the Related Art
Controlled delivery of beneficial agents, such as drugs, in the medical and veterinary fields, has been accomplished by a variety of methods, including implantable delivery devices such as implantable osmotic delivery devices and implantable diffusion controlled delivery systems. Osmotic delivery systems are very reliable in delivering a beneficial agent over an extended period of time called an administration period. In general, osmotic delivery systems operate by imbibing fluid from an outside environment and releasing corresponding amounts of beneficial agent from the delivery system.
Representative examples of various types of delivery devices are disclosed in U.S. Pat. Nos. 3,732,865; 3,987,790; 4,865,845; 5,059,423; 5,112,614; 5,137,727; 5,213,809; 5,234,692; 5,234,693; 5,308,348; 5,413,572; 5,540,665; 5,728,396; and 5,985,305, all of which are incorporated herein by reference. All of the above-cited patents generally include some type of capsule having at least a portion of a wall that selectively passes water into the interior of the capsule containing a water-attracting agent (also called an osmotic agent, an osmopolymer or osmoagent). The absorption of water by the water-attracting agent within the capsule reservoir creates an osmotic pressure within the capsule which causes a beneficial agent within the capsule to be delivered. The water-attracting agent may be the beneficial agent being delivered to the patient. However, in most cases, a separate agent is used specifically for its ability to draw water into the capsule.
When a separate osmotic agent is used, the osmotic agent may be separated from the beneficial agent within the capsule by a movable dividing member, such as a piston. The structure of the capsule is generally rigid such that as the osmotic agent takes in water and expands, the capsule does not expand. As the osmotic agent expands, the agent causes the movable dividing member to move, discharging the beneficial agent through an orifice or exit passage of the capsule. The beneficial agent is discharged through the exit passage at the same volumetric rate that water enters the osmotic agent through the semipermeable wall portion of the capsule.
The rate at which the beneficial agent is discharged from the delivery device is determined by many factors, including the type of water-attracting agent or osmotic agent, the permeability of the semipermeable membrane wall, and the size and shape of the exit passage. One manner in which the back diffusion of environmental fluid into the beneficial agent reservoir is controlled is by a flow moderator in the exit passage of the capsule, with the flow moderator generally consisting of a tubular passage having a particular cross-sectional area and length.
In known osmotic delivery systems, an osmotic tablet, such as salt, is placed inside the capsule and a membrane plug is placed in an open end of the capsule to provide a semipermeable barrier. The membrane plug seals the interior of the capsule from the exterior environment, permitting only certain liquid molecules from the environment to permeate through the membrane plug and into the interior of the capsule. The membrane plug is impermeable to items within the capsule including the osmotic agent and the beneficial agent. The rate at which the liquid permeates the membrane plug and enters the capsule varies depending upon the type of membrane material and the size and shape of the membrane plug. Further, the rate at which the liquid passes through the membrane plug controls the rate at which the osmotic agent expands to thereby drive the beneficial agent from the delivery system through the exit passage. Accordingly, the rate of delivery of the beneficial agent from the osmotic delivery system is controllable by varying the permeability coefficient of the membrane plug and/or the size of the membrane plug.
Some known osmotic delivery systems use injection molded membrane plugs featuring protruding circumferential sealing ribs that fit into matching circumferential grooves on the inside of the capsule (U.S. Pat. No. 6,113,938, which is incorporated herein by reference). The membrane plug is retained in the capsule by the sealing ribs, which usually requires the membrane to be inserted from the membrane end of the reservoir. Injection molded semipermeable membranes may be difficult to manufacture without internal stresses; thus performance may vary slightly from plug to plug. An additional drawback of known osmotic delivery systems is that the membrane plug itself is required to withstand the pressures created by the expansion of the osmotic engine. Other known osmotic delivery systems use membrane plugs with protruding circumferential sealing ribs but no matching circumferential grooves inside of the capsule. Still other known osmotic delivery systems use membrane plugs with no circumferential sealing ribs that fit into the capsule by friction fit. Still other known osmotic delivery systems use membrane plugs without any circumferential sealing ribs but with holes in the capsule into which the membrane plug can expand (WO99/33446, which is incorporated herein by reference). Known delivery systems preclude the use of a capsule having a pre-installed retaining feature covering or partially covering the membrane plug end of the capsule for keeping the membrane plug sealed in position. Consequently, in these systems, if a retaining feature other than the capsule grooves and matching ribs of the membrane plug is to be used, it must be assembled to the main capsule body, after the membrane plug is inserted. This requirement tends to increase the cost and complexity of a high pressure osmotic delivery system.
Accordingly, it is desirable to provide a delivery device that provides improved consistency and performance of the membrane material and also provides a feature for retaining the membrane material within the capsule under high pressure.